| 1. |
- Kessing, C. F., et al.
(författare)
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High Number of Activated CD8(+) T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection
- 2017
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Ingår i: Jaids-Journal of Acquired Immune Deficiency Syndromes. - 1525-4135. ; 75:1, s. 108-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Central nervous system (CNS) infiltration by CD8(+) T cells is associated with neuroinflammation in many neurodegenerative diseases, including HIV-associated dementia. However, the role of CD8(+) T cells in the CNS during acute HIV infection (AHI) is unknown. Methods: We analyzed the phenotype, gene expression, T cell receptor (TCR) repertoire, and HIV specificity of CD8(+) T cells in cerebrospinal fluid (CSF) of a unique cohort captured during the earliest stages of AHI (n = 26), chronic (n = 23), and uninfected (n = 8). Results: CSF CD8(+) T cells were elevated in AHI compared with uninfected controls. The frequency of activated CSF CD8(+) T cells positively correlated to CSF HIV RNA and to markers of CNS inflammation. In contrast, activated CSF CD8(+) T cells during chronic HIV infection were associated with markers of neurological injury and microglial activation. CSF CD8(+) T cells in AHI exhibited increased functional gene expression profiles associated with CD8(+) T cells effector function, proliferation, and TCR signaling, a unique restricted TCR Vbeta repertoire and contained HIV-specific CD8(+) T cells directed to unique HIV epitopes compared with the periphery. Conclusions: These results suggest that CSF CD8(+) T cells in AHI expanding in the CNS are functional and directed against HIV antigens. These cells could thus play a beneficial role protective of injury seen in chronic HIV infection if combination antiretroviral therapy is initiated early.
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| 2. |
- Peluso, Michael J, et al.
(författare)
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Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection.
- 2017
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Ingår i: AIDS (London, England). - 1473-5571. ; 31:2, s. 247-252
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Tidskriftsartikel (refereegranskat)abstract
- To characterize cerebrospinal fluid (CSF) YKL-40, a unique biomarker that reflects activation of microglial cells, in acute (AHI) and chronic HIV-1 infection (CHI) and to determine the effect of treatment initiation on levels of this marker.Cross-sectional study of two groups of HIV-infected participants at baseline and follow-up timepoints.AHI (n=33) and CHI (n=34) participants underwent CSF and blood sampling before treatment initiation with combination antiretroviral therapy (cART) and at follow up on cART in a subset of these individuals (6 months in AHI participants [n=24], 1 year in CHI participants [n=10]). Measured parameters were analyzed at each timepoint. Analyses employed Mann-Whitney tests and Spearman correlations.Baseline median YKL-40 was higher in CHI than AHI (96844 versus 80754 ng/L; p=0.011). Elevations in the CHI group relative to the AHI group persisted at follow-up despite treatment (87414 versus 66130ng/L; p=0.003). In untreated CHI, YKL-40 correlated with neopterin (r=0.51, p=0.0025), chemokine (CXC-motif) ligand-10 (r=0.44, p=0.011), and neurofilament light chain (r=0.56, p=0.0008) in CSF.This study is the first to describe the dynamics of CSF YKL-40 in two groups of HIV-infected individuals before and after cART and demonstrates the value of this marker in understanding HIV neuropathogenesis. The results suggest the utility of further exploring the prognostic value of YKL-40, particularly in individuals with early HIV infection or those initiating treatment during CHI.
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| 3. |
- Cooper, Steven J., et al.
(författare)
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Exploring Snowfall Variability through the High-Latitude Measurement of Snowfall (HiLaMS) Field Campaign
- 2022
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 103:8, s. E1762-E1780
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Tidskriftsartikel (refereegranskat)abstract
- The High-Latitude Measurement of Snowfall (HiLaMS) campaign explored variability in snowfall properties and processes at meteorologically distinct field sites located in Haukeliseter, Norway, and Kiruna, Sweden, during the winters of 2016/17 and 2017/18, respectively. Campaign activities were founded upon the sensitivities of a low-cost, core instrumentation suite consisting of Micro Rain Radar, Precipitation Imaging Package, and Multi-Angle Snow Camera. These instruments are highly portable to remote field sites and, considered together, provide a unique and complementary set of snowfall observations including snowflake habit, particle size distributions, fall speeds, surface snowfall accumulations, and vertical profiles of radar moments and snow water content. These snow-specific parameters, used in combination with existing observations from the field sites such as snow gauge accumulations and ambient weather conditions, allow for advanced studies of snowfall processes. HiLaMS observations were used to 1) successfully develop a combined radar and in situ microphysical property retrieval scheme to estimate both surface snowfall accumulation and the vertical profile of snow water content, 2) identify the predominant snowfall regimes at Haukeliseter and Kiruna and characterize associated macrophysical and microphysical properties, snowfall production, and meteorological conditions, and 3) identify biases in the HARMONIE-AROME numerical weather prediction model for forecasts of snowfall accumulations and vertical profiles of snow water content for the distinct snowfall regimes observed at the mountainous Haukeliseter site. HiLaMS activities and results suggest value in the deployment of this enhanced snow observing instrumentation suite to new and diverse high-latitude locations that may be underrepresented in climate and weather process studies.
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| 4. |
- Flynn, E. D., et al.
(författare)
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Transcription factor regulation of eQTL activity across individuals and tissues
- 2022
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 18:1, s. e1009719-
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Tidskriftsartikel (refereegranskat)abstract
- Tens of thousands of genetic variants associated with gene expression (cis-eQTLs) have been discovered in the human population. These eQTLs are active in various tissues and contexts, but the molecular mechanisms of eQTL variability are poorly understood, hindering our understanding of genetic regulation across biological contexts. Since many eQTLs are believed to act by altering transcription factor (TF) binding affinity, we hypothesized that analyzing eQTL effect size as a function of TF level may allow discovery of mechanisms of eQTL variability. Using GTEx Consortium eQTL data from 49 tissues, we analyzed the interaction between eQTL effect size and TF level across tissues and across individuals within specific tissues and generated a list of 10,098 TF-eQTL interactions across 2,136 genes that are supported by at least two lines of evidence. These TF-eQTLs were enriched for various TF binding measures, supporting with orthogonal evidence that these eQTLs are regulated by the implicated TFs. We also found that our TF-eQTLs tend to overlap genes with gene-by-environment regulatory effects and to colocalize with GWAS loci, implying that our approach can help to elucidate mechanisms of context-specificity and trait associations. Finally, we highlight an interesting example of IKZF1 TF regulation of an APBB1IP gene eQTL that colocalizes with a GWAS signal for blood cell traits. Together, our findings provide candidate TF mechanisms for a large number of eQTLs and offer a generalizable approach for researchers to discover TF regulators of genetic variant effects in additional QTL datasets.
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